The proposed studies are a Renewal Application on "Molecular Genetic Studies of the Human T-Cell Leukemia Viruses". The human T-cell leukemia viruses, HTLV-I and HTLV-II, are the only known oncogenic retroviruses of man, and are the etiologic agents of specific T-cell malignancies, adult T-cell leukemia, and possibly some forms of a typical hairy-cell leukemia. The processes of HTLV replication and the mechanisms of T-cell transformation are unique among animal retroviruses. Over the past several years, we and other investigators have identified transcriptional activating functions in the HTLV genome, and identified the protein product of the gene encoding these functions. In addition, we have characterized the structure, expression and some functions of these trans-acting functions. The studies proposed in this Application are a direct extension of these previous studies. The specific goals are: 1. To further characterize cis-acting functions of the HTLV LTR responsive to trans-acting viral functions. 2. To further characterize trans-acting viral functions by mutagenesis. 3. To identify and characterize viral functions responsible for T- cell immortalization/transformation. We have established a number of unique reagents and approaches, particularly for HTLV-II, and these will be applied to the proposed studies.